Probabilistic controllability approach to metabolic fluxes in normal and cancer tissues

Abstract

Recent research has shown that many types of cancers take control of specific metabolic processes. We compiled metabolic networks corresponding to four healthy and cancer tissues, and analysed the healthy–cancer transition from the metabolic flux change perspective. We used a Probabilistic Minimum Dominating Set (PMDS) model, which identifies a minimum set of nodes that act as driver nodes and control the entire network. The combination of control theory with flux correlation analysis shows that flux correlations substantially increase in cancer states of breast, kidney and urothelial tissues, but not in lung. No change in the network topology between healthy and cancer networks was observed, but PMDS analysis shows that cancer states require fewer controllers than their corresponding healthy states. These results indicate that cancer metabolism is characterised by more streamlined flux distributions, which may be focused towards a reduced set of objectives and controlled by fewer regulatory elements.